Differential infectious entry of human influenza A/NWS/33 virus (H1N1) in mammalian kidney cells

In this report we focused our interest on the early events of the replication cycle of NWS/33 human influenza A (NWS) virus in MDCK (canine), LLC-MK2 (simian), and NSK (swine) kidney cells, with different susceptibility upon infection. We have previously demonstrated that actin organization induces restriction to viral replication during the early stages of NWS virus infection in simian kidney cells. To explore how cell endocytic mechanisms are hijacked by NWS virus and may modulate the outcome of viral infection, the effect of drugs affecting selectively the entry via clathrin-coated pits, caveolar/raft-dependent endocytosis and macropinocytosis was analyzed. Results point to critical differences in terms of internalization pathways exploited by NWS virus to enter the examined cell models. Moreover, we show that some ways of entry do not allow an effective virus internalization, depending on the cell type. Understanding how specific cell functions/components may regulate early phases of viral replication allows us to deepen our knowledge on influenza virus infection and provides new insights for anti-viral researches.